title: Irditoxin, a novel covalently linked heterodimeric three-finger toxin with high taxon-specific neurotoxicity.
abstract: A novel heterodimeric three-finger neurotoxin, irditoxin, was isolated from venom of the brown treesnake Boiga irregularis (Colubridae). Irditoxin subunit amino acid sequences were determined by Edman degradation and cDNA sequencing. The crystal structure revealed two subunits with a three-finger protein fold, typical for "nonconventional" toxins such as denmotoxin, bucandin, and candoxin. This is the first colubrid three-finger toxin dimer, covalently connected via an interchain disulfide bond. Irditoxin showed taxon-specific lethality toward birds and lizards and was nontoxic toward mice. It produced a potent neuromuscular blockade at the avian neuromuscular junction (IC(50)=10 nM), comparable to alpha-bungarotoxin, but was three orders of magnitude less effective at the mammalian neuromuscular junction. Covalently linked heterodimeric three-finger toxins found in colubrid venoms constitute a new class of venom peptides, which may be a useful source of new neurobiology probes and therapeutic leads.
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, Science Dr. 4, Singapore 117543.
authors.forename: Joanna
authors.initials: J
authors.lastname: Pawlak
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Mackessy
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Sixberry
authors.forename: Enrico A
authors.initials: EA
authors.lastname: Stura
authors.forename: Marie Hélène
authors.initials: MH
authors.lastname: Le Du
authors.forename: Renée
authors.initials: R
authors.lastname: Ménez
authors.forename: Chun Shin
authors.initials: CS
authors.lastname: Foo
authors.forename: André
authors.initials: A
authors.lastname: Ménez
authors.forename: Selvanayagam
authors.initials: S
authors.lastname: Nirthanan
authors.forename: R Manjunatha
authors.initials: RM
authors.lastname: Kini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D017812:Colubridae / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000235:genetics; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D012910:Snake Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D013045:Species Specificity; D040681:Structural Homology, Protein
chemical_list: D018076:DNA, Complementary; D009498:Neurotoxins; D021122:Protein Subunits; D012910:Snake Venoms